Biology subjects

Lee, M. M.

Publications and source records attributed to Lee, M. M..

6 recordsLinked to original sources

bioRxiv2023

Neural bases of reading fluency: A systematic review and meta-analysis

Reading fluency, the ability to read quickly and accurately, is a critical marker of successful reading and is notoriously difficult to improve in reading disabled populations. Despite its importance to functional literacy, fluency is a relatively under-studied aspect of reading, and the neural correlates of reading fluency are not well understood. Here, we review the literature of the neural correlates of reading fluency and rapid automatized naming (RAN), a task that is robustly related to reading speed. In a qualitative review of the neuroimaging literature, we evaluated structural and functional MRI studies of reading fluency in readers ranging in skill levels. This was followed by a quantitative activation likelihood estimate (ALE) meta-analysis of fMRI studies of reading fluency and RAN measures. We anticipated that reading speed, relative to untimed reading and reading-related tasks, would harness ventral reading pathways that are thought to enable the fast, visual recognition of words. The qualitative review showed that speeded reading taps the entire canonical reading network. The meta-analysis, which focused on in-scanner reading fluency measures, indicated a stronger role of the ventral reading pathway in fluent reading. Both reviews identified regions outside the canonical reading network that contribute to reading fluency, such as the bilateral insula and superior parietal lobule. We suggest that fluent reading engages both domain-specific reading pathways as well as domain-general regions that support overall task performance and discuss future avenues of research to expand our understanding of the neural bases of fluent reading.

neuroscience↗

bioRxiv2023

Dietaryindex: A User-Friendly and Versatile R Package for Standardizing Dietary Pattern Analysis in Epidemiological and Clinical Studies

BackgroundFew standardized and open-source tools exist for calculating dietary pattern indexes from dietary intake data in epidemiological and clinical studies. Miscalculations of dietary indexes, with suspected erroneous findings, are occasionally noted in the literature. ObjectiveThe primary aim is to develop and validate dietaryindex, a user-friendly and versatile R package that standardizes the calculation of dietary indexes. MethodsDietaryindex utilizes a two-step process: an initial calculation of serving size for each food and nutrient category, followed by the calculation of individual dietary indexes. It includes generic functions that accept any preprocessed serving sizes of food groups and nutrients, with the standard serving sizes defined according to the methodologies used in well-known prospective cohort studies. For ease of use, dietaryindex also offers one-step functions that directly reference common datasets and tools, including the National Health and Nutrition Examination Survey (NHANES) and Block Food Frequency Questionnaire, eliminating the need for data preprocessing. At least two independent researchers validated the serving size definitions and scoring algorithms of dietaryindex. ResultsDietaryindex can calculate multiple dietary indexes of high interest in research, including Healthy Eating Index (HEI) - 2020, Alternative Healthy Eating Index 2010, Dietary Approaches to Stop Hypertension Index, Alternate Mediterranean Diet Score, Dietary Inflammatory Index, American Cancer Society 2020 dietary index, and Planetary Health Diet Index from the EAT-Lancet Commission. In our validation process, dietaryindex demonstrated full accuracy (100%) in all generic functions with two-decimal rounding precision in comparison to hand-calculated results. Similarly, using NHANES 2017-2018 data and ASA24 and DHQ3 example data, the HEI2015 outputs from dietaryindex aligned (99.95% - 100%) with results using the SAS codes from the National Cancer Institute. ConclusionsDietaryindex is a user-friendly, versatile, and validated informatics tool for standardized dietary index calculations. We have open-sourced all the validation files and codes with detailed tutorials on GitHub (https://github.com/jamesjiadazhan/dietaryindex).

bioinformatics↗

bioRxiv2020

Autocrine Signaling by Receptor Tyrosine Kinases in Urothelial Carcinoma of the Bladder

Comprehensive characterizations of bladder cancer (BCa) have established molecular phenotype classes with distinct alterations and survival trends. Extending these studies within the tyrosine kinase (TK) family to identify disease drivers could improve our use of TK inhibitors to treat specific patient groups or individuals. We examined the expression distribution of TKs as a class (n = 89) in The Cancer Genome Atlas (TCGA) muscle invasive BCa data set (n >400). Patient profiles of potentially oncogenic alterations (overexpression and/or amplification) clustered TKs into 3 groups; alterations of group 1 and 3 TKs were associated with significantly worse patient survival relative to those without alterations. Many TK pathways induce epithelial-to-mesenchymal transition (EMT), which promotes tumor invasiveness and metastasis. Overexpression and/or amplification among 9 EMT transcriptional activators occurred in 43% of TCGA cases. Co-occurring alterations of TKs and EMT transcriptional activators involved most group 1 TKs; 24% of these events were associated with significantly worse patient survival. Co-occurring alterations of receptor TKs and their cognate ligands occurred in 16% of TCGA cases and several BCa-derived cell lines. Suppression of GAS6, MST1 or CSF1, or their respective receptors (AXL, MST1R and CSF1R), in BCa cell lines was associated with decreased receptor activation, cell migration, cell proliferation and anchorage independent cell growth. These studies reveal the patterns and prevalence of potentially oncogenic TK pathway-related alterations in BCa and identify specific alterations associated with reduced BCa patient survival. Detection of these features in BCa patients could better inform TK inhibitor use and improve clinical outcomes.

cancer biology↗

bioRxiv2020

Protein arginine methyltransferase 5 promotes metastasis via enhancing EGFR transcription and modulating AKT1 activation by methylation

Protein arginine methyltransferase 5 (PRMT5) regulates a wide range of physiological processes, including cancer cell proliferation and metastasis, by generating symmetric di-methyl-arginine marks on histones and non-histone proteins. Here, we report that PRMT5 directly regulates epidermal growth factor receptor (EGFR) transcription to control EGF stimulated EGFR signaling. Furthermore, PRMT5 modulates protein kinase B (AKT) activation by methylation of AKT1 Arg 15, which is required for its subsequent phosphorylation at AKT1 Thr 308 and Ser 473. The PRMT5/EGFR/AKT axis converges to regulate transcription factors ZEB1, SNAIL, and TWIST1 to promote the epithelial-mesenchymal transition (EMT), in the manner that EGFR and AKT1 compensate each other to support tumor cell invasion and metastasis. Inhibiting PRMT5 methyltransferase activity with a small molecule inhibitor attenuated primary tumor growth and prevented hepatic metastasis in aggressive in vivo tumor models. Collectively, our results support the use of PRMT5 based therapies for metastatic cancer.

cancer biology↗

bioRxiv2019

Human embryoid bodies model basal lamina assembly and muscular dystrophy

The basal lamina is a specialized sheet of dense extracellular matrix (ECM), linked to the plasma membrane of specific cell types in their tissue context, that serves as a structural scaffold for organ genesis and maintenance. Disruption of the basal lamina and its functions is central to many disease processes, including cancer metastasis, kidney disease, eye disease, muscular dystrophies, and specific types of brain malformation. The latter three pathologies occur in the dystroglycanopathies, which are caused by dysfunction of the ECM receptor dystroglycan. However, opportunities to study the basal lamina in various human disease tissues are restricted due to its limited accessibility. Here, we report the generation of embryoid bodies from human induced pluripotent stem cells to model basal lamina formation. Embryoid bodies cultured via this protocol mimic pre-gastrulation embryonic development, consisting of an epithelial core surrounded by a basal lamina and a peripheral layer of ECM-secreting endoderm. In dystroglycanopathy patient embryoid bodies, electron and fluorescence microscopy revealed ultrastructural basal lamina defects and reduced ECM assembly. By starting from patient-derived cells, these results establish a method for the in vitro synthesis of patient-specific basal lamina and recapitulate disease-relevant ECM defects seen in muscular dystrophies. Finally, we applied this system to evaluate an experimental ribitol supplement therapy on genetically diverse dystroglycanopathy patient samples.

cell biology↗

bioRxiv2017

Population-scale organization of cerebellar granule neuron signaling during a visuomotor behavior

Granule cells at the input layer of the cerebellum comprise over half the neurons in the human brain and are thought to be critical for learning. However, little is known about granule neuron signaling at the population scale during behavior. We used calcium imaging in awake zebrafish during optokinetic behavior to record transgenically identified granule neurons throughout a cerebellar population. A significant fraction of the population was responsive at any given time. In contrast to core precerebellar populations, granule neuron responses were relatively heterogeneous, with variation in the degree of rectification and the balance of excitation versus inhibition. Functional correlations were strongest for nearby cells, with weak spatial gradients in the degree of rectification and excitation. These data open a new window upon cerebellar function and suggest granule layer signals represent elementary building blocks underrepresented in core sensorimotor pathways, thereby enabling the construction of novel patterns of activity for learning.\n\nSIGNIFICANCE STATEMENTCerebellar processing is important for a variety of fine motor tasks and sensorimotor adaptations, and a growing body of evidence indicates a prominent role in cognitive control. However, it has been challenging to understand cerebellar function during behavior because of difficulties in recording from cerebellar granule neurons, the most populous neuron type in the brain. We use population-scale optical imaging in the larval zebrafish to compare precerebellar activity to granule cell signaling. Our results suggest a behaviorally relevant expansion of precerebellar signaling representations at the granule layer of the cerebellum.

neuroscience↗